Process of producing n-aralkyl-amino-phenols



Patented Dec. 1936 UNITED STATES PROCESS OF PRODUCING N-ARALKYL- AliflNO-PHENOLB Miles A. Dahlen and Richard G. Clarkson, Wilmington, Del., and Martin E. P. Friedrich, Oarneys Point, N. 1., assignors to E. I. du Pont de Nemours & Company, Wilmington, Dcl., a corporation of Delaware No Drawing. Application February 6, 1934,

L Serial No. 710.032

10 Claims. (01. 260-128) This invention relates to aromatic compounds containing as a substituent a radical in which the nitrogen atom is linked to a phev nolic nucleus, more particularly N-aralkyl-r aminophenols, and a process for the production thereof. I

This application is a continuation-in-part of our co-pending application Serial No. 6'71,280 filed May 15, 1933 (now abandoned).

It is known that N-aralkyl-aminophenols may be prepared by the action of aralkyl-halides upon primary amino-phenols. For example, N-benzylpara-aminophenol may be prepared by the action of benzyl-ehloride on para-aminophenol. This method of preparing the N-aralkyl-aminophenols oilers the widely recognized difilculty of producing as by-products often of veryv little value the N-diaralkyI-aminophenols. I'hus, in the production of N-benzyl-para-aminophenol by this method large quantities of N-dibenzyl-paraaminophenol are obtained. Furthermore, the separation of the desired N-monoaralkyl-aminophenols from the N-diaralkyl derivatives and from the unreacted aminophenol is usually attended with many difficulties. As a result, this process is not a suitable method for the economical preparation of the N-aralkyl-aminophenols, particularly when products of high purity are desired.

It has alsobeen proposed to produce the N- aralkyl-aminophenols from the corresponding N- aralkylidene-aminophenols by heating them in the presence of an alkaline reducing medium such as, for example, a metal and an alkali metal hydroxide. Similarly, the production of the N- aralkyl-aminophenols from the N-aralkylideneaminophenols by the action of metallic sodium and alcohol has been proposed. Electrochemical methods of converting the N-aralkylidene-aminophenol to the corresponding N-aralkyl-aminophenol have also been suggested. These methods present many difliculties on account of the instability of the N-aralkyl-aminophenols under the acidic or alkaline conditions usually present.

One of the disadvantages is the partial hydrolysis .during the reaction of a portion of the N- aralkylidene-aminophenol to the parent aldehyde and aminophenol. As a result, the yields of the desired N-aralkyl-aminophenols are often low and the product may be contaminated with impurities such as an aminophenol.

It is an object oi this invention to provide a new and improved process for the productim of compounds having a radical in which the nitrogen atom is attached to a phenolic nucleus. Another object is the provision of a new and improved process for the'production of N-aralkyl-aminophenols. A further object is the provision 01' an improved process in which prodnets of the character above described may be obtained in excellent yields and in a high state of purity. A still further object is the production or products of the character described by a process which may be readily and economically'operated on a large scale. An additional object is the provision of a process which may be operated practically with raw materials containing impurities. Other objects will appear hereinafter. 7

These objects are accomplished according to this invention whereby compounds containing the radical H in which the nitrogen atom is attached to a phenolic nucleus, to a catalytic hydrogenation in the liquid phase in the presence of a non-polar, nonhydrogenated organic solvent such as, for example, benzene and/or toluene.

The invention further contemplates in its more-specific aspects the application of a process of the character above described under such conditions of temperature and pressure that it may be carried out commercially with starting materials containing impurities.

While the invention is susceptible to considerable variation and modification in the manner of its practical application, particularly as regards the proportions of materials, temperatures, pressures and the exact method of procedure, the following examples, in which the parts are by weight, will serve to illustrate how the rocess may be practised.

Example I o An autoclave was charged with 394 parts of dry-tolucne,- 197 parts of dry N-benzal-paraaminophenol and 4 parts-of an active nickel-onkieselguhr catalyst. The air was displaced by hydrogen, the mass heated to 100 C. with agitation, and a pressure of 400 pounds per square inch of hydrogen applied. Rapid absorption of hydrogen took place, and additional quantities of the gas were added tomaintain the above pressure. The temperature was held at C.

to C. during the entire hydrogenation.

When reduction was complete, as shown by no further absorption of hydrogen, the mass was. ,flltered at 100 C. through a pre-heated filter to ditional 15 to 20 parts of material of slightly inferior quality were obtained by the second crystallization. The total yield of product was about 95% of the theory, based on N-benzal-p'ara aminophenol used. I

Example I! The process of Example I was repeated, substituting 800 parts of benzene for the 394 parts of toluene as the hydrogenating medium. After removal of catalyst by filtration, the benzene was distilled oil leaving the crude N-benzyl-paraaminophenol as a semi-solid residue. The crude product was purified by crystallization from alcohol. A yield of approximately 95% of the theory, based on benzal compound reduced, was obtained.

According to procedures similar to those described in the examples, a large number of other products may -be prepared, all of which are. characterized by having a radical ii l inwhich the nitrogen atom is attached to a carbon atom of a phenolic nucleus. The following formula is illustrative of the type of compounds produced:

ti... 1!: Jr

these compounds being obtained from compounds having the following general formula:

methoxy, ethoxy, etc.), aryloxy (e. g., phenoxy, naphthoxy, etc.), aryl '(e. g., phenyl, naphthyl, etc.) hydrox'y'and halogens (e. g., chlorine, bromine, etc.), and R represents hydrogen, albl. aralkyl (benzyl and the like), aryl, hydroaryl (cyclopentyl, cyclohexyl, hydronaphthyl, etc.), and heterocyclic (furfuryl, morpholyl, hydrothiazyl, quinolyl and the like) radicals. Where R is a carbon radical, it may contain substituents other than hydrogen. Thus, where R is an aryl nucleus, it may contain substituents such vas, for example, alkyl, alkoxy and halogen groups.

Specific examples of these products and raw materials from which they may .be prepared, in addition to the products given in the. examples,

are:

Product Prepared from N-benzyl-atbo-aminophenol N-benzaiortho-eminophencl. N-parf-metbyl-benzyl-ort N-para-tolual-ortho-amino amlnophsnol. phenol. N-(f-chloro-bensyh-paras N-(2'-chloro-benzal)-paraaminop aminopbenol. N-bemyl-meta-amino-pera- N-bensal-mete-amino-para- N-bOlll l-pare-amino-guiacol..- N benral-para-amino-guiacol. 'N- -lnetlmox'y-henzyl-fial'a- N anisal para chloro o-aminopbeno phenol. N-heptyl-para-eminophenol N heptylidene para amino N-heptyl-orthoaminophenol..." N mptl ylldene ortho amino 0 N-ethyl-para-eminopbenol-.- N-- eth iidene ortho amino N hexahydrobenzylp... N hesahydrobeural para aminopllrenol. hm aminophenol. m be l my para-amino JurhJraI-pare-am o no N (4' '-methyl bensy l) N (4 methyl benzgl) para aminop amino N-(4'-methory-bensyl) -3- N-(4-methory-benral)-3- amino-fi-hydroxy-toluene. amino-c-hydrory-tolmne. N-(2'-chloro-benzyl)-crtho- N-(2-chioro-benral)-ortho- Narai nolplol. m uahiopbenol. bow) -y xybenz -m x- -mtaamlnophenol. N-(4-phenox -benzyl)-para- N-(4'-p -bensal)-panlm am I I .4. N-(alha-nehthl-methl- N-al-nahthal-pany p p N (4' phenyl benlyl) para N (4 renal) ortho amino amino henol. phenol. N-benzy -l-smino-7-na%hthoi..-. l-bensal-aminoJ-naphthol. N-benzyl-i-amino-lydroxy- 4 benI-al amino l hydrory anthracene. anthracene.

- y- -paraua-amnomind-plume]. phenol.

Likewise, the invention is applicable to the n x a' cfn-n \OH ll from compounds having the following formula:

1: x n'- J=N--R OH on in which R, R and x have the foregoing signification, and m is an integer more than one. An example of a product falling within this general formula is para'-xylylene-bis-para-aminophenol prepared from terephthalal-para-aminophenol.

The method of procedure in eii'ecting the hydrogeneration is subject to variation but preferably involves dissolving and/or suspending the raw material in the solvent in the presence of an active hydrogenating catalyst, and subjecting this mixture to the action of hydrogen under pressure and at elevated temperatures.

The choice of the solvent has a decided eifect upon the results obtained. As an illustration. 15

N-ben'zyl-para-aminophenol may be obtained in 95% yield by the reaction of hydrogen with N- ben'zal-para-aminophenol according to the method described in the examples in which aromatic hydrocarbons such as benzene and toluene are used as solvents, whereas the'yield is of the order of 50% when the reaction is carried out in the presence of ethyl alcohol. The non-hydrogenated solvents such as benzene and toluene also pos-' sess certain distinct advantages over hydrogenated solvents such as, for example, decahydronaphthalene, hexahydrobenzene and the) like. Thus, the non- -hydrogenated solvents are, in gen- I eral, better solvents for both the benzal and the benzyl compounds and the operation can be eifected under more concentrated conditions, giving a larger amount of product per unit of capacity. The non-hydrogenated solvents are also advantageous from the economic standpoint. Examples of other non-hydrogenated solvents which may be mentioned are the xylenes and naphthalene.

The nature and quantity of the catalyst used is subject to variation. In general, the more .active the catalyst and the higher the pressure used, the smaller the quantity of catalyst required to effect reduction in a given period of time. The catalyst may be carried on a support such as, for example, kieselguhr, carborundum and the like. Itmay be distributed throughout the reaction mixture or fixed on a carrier in such a way that its position is more or less permanent. An active nickel catalyst, for example, active'nickel supported on kieselguhr, is preferably employed but other catalysts, especially of the iron group such as active iron or cobalt, may be used. Ifv

desired, the catalyst may be in the form of a metallic wool or screen. The catalyst may also consist of a salt of a hydrogenating metal such as, for example, cobalt, copper, iron, silver or nickel, together with a promoting oxide. Such a catalyst is copper chromite which may be used in place of nickel, either with or without previous reduction.

The temperatures and pressures of operation are subject to variation but, in general, it is preferable to employ a temperature of at least 90 C. and preferably not more than 140 C., and a pressure of at least atmospheres and preferably not v more than about 100 atmospheres. Under these conditions the solvent, such as benzene or toluene, is not substantially hydrogenated and may be separated from the product and continuously re-. used in the process with no substantial loss of efliciency. By employing rather strenuous conditions of pressure (that is, at least 10 atmospheres) it is possible to carry out the process on a commercial scale with starting materials which contain small amounts of impurities such as, for example, iron, iron oxide, lead, lead oxide, aluminum salts, particularly in the form of the hydroxides and sulfates, sulfur in the form of sulfates, and small amounts of halogen compounds. This isof particular advantage because starting materials of the character described are now obtainable by a commercially practicable method, as outlined in U. S. Patent No. 2,027,902 granted to M. A.

Dahlen.

The method of isolating the product from the hydrogenation mass is usually varied in accordance with its physical and chemical properties.

Where the catalyst is present in the reaction mass, it may be separated in any suitable manner, for example, by filtration. The desired product may then be recovered from the filtrate by crystallization or in some other suitable way, such as distillation, of the solvent followed by recrystallization from anotherv or the .same solvent.

The products of the invention had many uses,

among which may be'mentioned the addition to gasoline to prevent gum formation and oxidation, the addition to rubber to prevent oxidation,

and the addition to fats, oils, waxes and similar substances to increase their stability. Many of stances which, according to prior art methods,

have been prepared only with the greatest difflculty and in relatively low yields. Thus, the N-mon'oaralkyl-aminophenols may be prepared in accordance with the process of the present invention without substantial formation of byproducts which contaminate the product .and decrease the yields. In the production of products of this type, therefore, the invention ofiers many advantages as distinguished from processes in which relatively large proportions of impurities such as diaralkyl derivatives and aminophenol or other hydrolytic decomposition products are formed. Other advantages have been given above.

The compounds subjected to hydrogenation in accordance withthe present invention may be termed .Schifls bases of aromatic aminophenols in which the aromatic 'nuclei are devoid of reducible substituents.

As many apparently widely different embodiments of this invention may be made without departing from the spirit and scope thereof, it is to be understood that we do not limit ourselves to,

the specific embodiments'thereof except as defined in the following claims.

We claim:

1. In a process of producing N-aralkyl-aminophenols, the step which comprises subjecting an N-aralkylidene-aminophenol to catalytic hydrogenation in the presence of a base metal catalyst in a liquid aromatic hydrocarbon under super-atmospheric temperature and pressure conditions insufliciently high to materially hydrogenate the liquid aromatic hydrocarbon.

2. In a process of producing N-aralkyl-aminophenols, the step which comprises subjecting an 3 drogenation in the presence of a base metal catalyst in a liquid aromatic hydrocarbon at a temperature within the range of about 90 C. to about 140 C. and a pressure within the range of about 10 to about 100 atmospheres.

4. In a process of producing N-benzyl-paraaminophenol, the step which comprises subjectv ,-w ithin the range of about 10. to about 100 atmo's- 'pheres.

- 5. The process of claim 4 in which benzene is used as a solvent medium.

6. The process oiclaim 4 "in which toluene is used as a solvent medium.

7. The process of producing N-benzyl-paraaminophenol which comprises reacting N-benzalpara-aminophenol with hydrogen in the pres-- ence of an active nickel-on-kieselguhr catalyst and benzene, while maintaining a temperature- 0! about-100 C. and a pressure of about 400 pounds per square inch.

8'. The process which comprises subjecting 20 Schifls bases of aromatic aminophenols in which the aromatic nuclei are devoid of reducible substituents to catalytic hydrogenation :in the presence oi a basefmetallza,, phase in ,a liquid aromatic hydr -benzene series.

i in liquid superatmospheric temperature and pressure coneditions insuiliciently high to materially hydrogenate said liquid aromatic hydrocarbon.

9. The process of claim 8 in which the liquid aromatic hydrocarbon is-a hydrocarbon oi the 10. The process orproducing N-benzyl-paraaminophenol which comprises subjecting N- benzal-para-aminophenol in catalytic hydrogenation in the presence. oi. a base metal catalyst in a liquid aromatic hydrocarbon solvent Ior N-benzyl-para-aminophenol under superstmospheric temperature and pressure conditions insumciently high to hydrogenate said' liquid aromatic hydrocarbon.

muss A. Dam. RICHARD G. cmnxson. MARTIN E. P. FRIEDRICH. 

